BIOMATERIALS
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2016
·
IF 8.387
Zi-Fei Zhou,Tuan-Wei Sun,Feng Chen,Dong-Qing Zuo,Hong-Sheng Wang,Ying-Qi Hua,Zheng-Dong Cai,Jun Tan
Biocompatibility, biodegradability and bioactivity are significantly important in practical applications of various biomaterials for bone tissue engineering . Herein, we develop a functional inorganic-organic hybrid system of calcium phosphate-phosphorylated adenosine (CPPA). Both calcium phosphate and phosphorylated adenosine molecules in CPPA are fundamental components in mammalians and play important roles in biological metabolism. In this work, we report our three leading research qualities: (1) CPPA hybrid microspheres with hollow and porous structure are synthesized by a facile one-step microwave-assisted solvothermal method; (2) CPPA hybrid microspheres show high doxorubicin loading capacity and pH-responsive drug release properties, and demonstrate positive therapeutic effects on six osteosarcoma cell lines in vitro and a mouse model of 143B osteosarcoma subcutaneous tumor in vivo ; (3) CPPA hybrid microspheres are favorable to promote osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) by activating the AMPK pathway, with satisfactory evidences from cellular alkaline phosphatase staining, alizarin red staining, real time PCR and western analysis. The as-prepared CPPA hybrid microspheres are promising in anti-osteosarcoma and bone regeneration , which simultaneously display excellent properties on drug delivery and osteogenic differentiation of hBMSCs.
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DOI
PubMed
高影响因子
Materials Today
·
2020
·
IF 26.416
Liang Ma,Xiaobo Feng,Hang Liang,Kun Wang,Yu Song,Lei Tan,Bingjin Wang,Rongjin Luo,Zhiwei Liao,Gaocai Li,Xiangmei Liu,Shuilin Wu,Cao Yang
After an osteosarcoma excision, recurrence, large bone defects, and soft tissue injury are significant challenges for clinicians. Conventional treatment by implanting bone replacement materials can induce bone regeneration after surgery, but this does not prevent bleeding, promote soft tissue repair , or help destroy the residual tumor cells. We attempted to develop a new multifunctional scaffold, with the clinical goals of facilitating tumor cell death through thermal ablation and promoting osteogenesis. Accordingly, we first investigated the effect of nano-hydroxyapatite/graphene oxide (nHA/GO) composite particles with different proportions on human osteosarcoma cells (HOS), pre-osteoblastic MC3T3-E1 cells, and human bone marrow mesenchymal stem cells (hBMSC) with or without 808-nm near-infrared (NIR) light irradiation. Next, we fabricated a novel temperature-controlled multifunctional nano-hydroxyapatite/graphene oxide/chitosan (nHA/GO/CS) scaffold, which can effectively kill human osteosarcoma cells under 808-nm NIR irradiation by reaching a temperature of 48 °C and further promote osteogenesis of hBMSC at 42 ± 0.5 °C in coordination with nHA. This scaffold demonstrates the best post-operative bone volume/tissue volume (BV/TV) ratio performance (20.36%) 8 weeks after scaffold implantation in the cranial defects of rats. Further exploration has revealed that NIR irradiation may promote the osteogenesis of hBMSC with the addition of nHA by enhancing the BMP2/Smad signaling pathway. Further, this scaffold has a good hemostatic effect and facilitates soft tissue repair under irradiation. This novel photothermally controlled multifunctional scaffold, which not only kills human osteosarcoma cells but also facilitates tissue regeneration , is a promising clinical tool for treating tissue injuries from an osteosarcoma resection.
研究领域:
生物医学工程
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材料科学
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肿瘤学
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再生医学
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DOI
高影响因子
RSC Advances
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2018
·Vol. 8
·期 52
·29637-29644
·
IF 2.936
Minyu Zhu,Jinwei Ying,Chaowei Lin,Yu Wang,Kelun Huang,Yang Zhou,Honglin Teng
β-Escin exhibits anticancer effects on a panel of established cancer cells. However, the effects of β-escin on human osteosarcoma (OS) are still unknown. The aim of the present study was to investigate whether β-escin was effective against OS both in vivo and in vitro. Our results showed that β-escin induced dose- and time-dependent effects against MG-63, OS732, U-2OS, HOS and SAOS-2 cell proliferation. β-Escin also exhibited excellent anti-proliferative and pro-apoptotic effects in an established OS xenograft model. β-Escin and cytotoxic drugs, including cisplatin, methotrexate (MTX), doxorubicin (Dox) and ifosfamide (Ifos), synergistically inhibited proliferation of MG-63 and OS732 cells in vitro. Moreover, β-escin induced apoptotic death, activated caspase-3, caspase-8 and caspase-9, and regulated expression of Bax and Bcl-2 in MG-63 cells. In addition, our results showed that β-escin treatment reduced expression of p-PI3K, p-Akt and p-mTOR both in MG-63 cells and in an MG-63 xenograft OS model. Interestingly, SC79, which is an Akt activator, inhibited the anti-proliferative effects of β-escin on MG-63 cells. Taken together, our data support the conclusion that β-escin effectively inhibits OS proliferation both in vivo and in vitro. The inhibitory effect of β-escin, at least in part, is due to the inactivation of the PI3K/Akt signalling pathway.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
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2017
·Vol. 19
·期 9
·1-10
·
IF 2.02
Hu Xiaoming,Li Lihua,Lu Yao,Liu Cong,Lei Yangqing,Zhang Chengcheng,Yin Qingshui,Zhang Yu
Photothermal therapy (PTT) has attracted great attention in cancer therapy because of high efficiency and low side effect. The semiconductors have been proved to be ideal photothermal agents in the past years. Herein, we synthesized a novel hexahedron structure of polyvinyl pyrrolidone (PVP) coating CuS nanocrystals (NCs) by a facile hydrothermal method. The synthesized CuS NCs (150 nm for average length of edge and 125 nm for length of width) have good biocompatibility due to their PVP coating and strong absorption in the near infrared region. Moreover, the CuS NCs exhibit high photothermal conversion efficiency as well as good antibacterial effect. Notably, the proliferation of osteosarcoma cancer cells can be efficiently inhibited both in vitro and in vivo by the fatal heat with very low concentration of CuS NCs under the near infrared ray at a power density of 0.5 W/cm 2 . Therefore, the CuS-PVP NCs have great potential to work as an ideal photothermal and antibacterial agent in clinical applications.
研究领域:
生物医学工程
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肿瘤学
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材料科学
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DOI
高影响因子
Journal of Materials Chemistry B
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2022
·Vol. 10
·期 27
·5263-5271
·
IF 7.571
Peng Liu,Weifei Zhang,Jiapeng Deng,Yien Zheng,Jian Weng,Fei Yu,Deli Wang,Ming Zheng,Bin Kang,Hui Zeng
Sulfur dioxide (SO2) based gas therapy has received great attention recently. Nevertheless, it is still a challenge to fabricate a SO2 delivery system to achieve effective delivery and on-demand stimuli triggered release at tumor sites. Herein, a chain-shattering polymeric SO2 prodrug micelle system was fabricated for effective SO2 based gas therapy. First, an amphiphilic polymer (mPEG-P(HDI-DN)) was prepared by polycondensation of poly(ethylene glycol) methyl ether, hexamethylene diisocyanate and monomer containing SO2. mPEG-P(HDI-DN) can self-assemble into spherical micelles with a diameter of around 50–90 nm. Triggered release of SO2 from micelles can be achieved in the presence of GSH with the degradation of mPEG-P(HDI-DN) into small molecules. The in vitro experiment proved that mPEG-P(HDI-DN) micelles can enter into osteosarcoma cells and inhibit the growth of osteosarcoma cells by increasing the ROS level in cells. The in vivo experiments demonstrate that mPEG-P(HDI-DN) micelles can inhibit the growth of osteosarcoma effectively without obvious tissue toxicity. These results indicate that this chain-shattering polymeric SO2 prodrug micelle system is a promising candidate for effective SO2 based gas therapy.
研究领域:
药学
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肿瘤学
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生物材料学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Xiuying Liu,Yu Zhang,Hang Wu,Jingwen Tang,Jiao Zhou,Jiulong Zhao,Shige Wang
In this study, a methacrylic gelatin/oxidized dextran/montmorillonite‑strontium/polypyrrole (GOMP) hydrogel was prepared. The GOMP hydrogel had dual network structure which was formed through photoinitiator-initiated double bond polymerization and Schiff base reaction. The network structure led to a sustained release of the antitumor drug, doxorubicin (DOX). Polypyrrole introduced the conductivity and high photothermal conversion capacity to the GOMP hydrogel, which showed a photothermal conversion efficiency of 31.61 % under 808 nm laser radiation. The GOMP hydrogel had good swelling properties in solvents. Further study showed that the GOMP hydrogel had good biocompatibility and excellent biodegradability in vitro and in vivo. The experiments of in vitro tumor therapy and in vivo anti-tumor recurrence indicated that the DOX-loaded GOMP hydrogel had synergistic effects on tumor cell apoptosis based on chemotherapy and photothermal therapy. In addition, montmorillonite‑strontium (MMT-Sr) doped in the hydrogel not only improved the mechanical properties of the hydrogel but also promoted potential bone regeneration. The multifunctional DOX-loaded GOMP hydrogel with bone regeneration, photothermal therapy, and chemotherapy functions has great potential application for treating osteosarcoma.
研究领域:
生物材料学
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肿瘤学
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再生医学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2023
·
IF 10
Yu-ying Yang,Yuan Zheng,Jun-jin Liu,Zhuang-peng Chang,Yue-hua Wang,Yun-yun Shao,Rui-gang Hou,Xiao Zhang
Surgical resection is the most common approach for the treatment of osteosarcoma. However, two major complications, including residual tumor cells and large bone defects, often arise from the surgical resection of osteosarcoma. Discovering new strategies for programmatically solving the two above-mentioned puzzles has become a worldwide challenge. Herein, a novel one-step strategy is reported for natural phenolic acid planted nanohybrids with desired physicochemical properties and steerable photothermal effects for efficacious osteosarcoma suppression and bone healing. Nanohybrids are prepared based on the self-assembly of chlorogenic acid and gold nanorods through robust Au-catechol interface actions, featuring precise nanostructures, great water solubility, good stability, and adjustable hyperthermia generating capacity. As expected, on the one hand, these integrated nanohybrids can severely trigger apoptosis and suppress tumor growth with strong hyperthermia. On the other hand, with controllable mild NIR irradiation, the nanohybrids promote the expression of heat shock proteins and induce prominent osteogenic differentiation. This work initiates a brand-new strategy for assisting osteosarcoma surgical excision to resolve the blockage of residual tumor cells elimination and bone regeneration.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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材料科学
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组织工程
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Wenyi Wang,Junli Chang,Hongfeng Ruan,Xingyuan Sun,Fulai Zhao,Peng Zhao,Chujie Zhou,Junjie Tong,Suxia Guo,Qi Shi,Yongjun Wang,Weian Zhang,Yanping Yang
Cancer is a global leading cause of death, with nearly 10 million people dying from cancer in 2020. Photodynamic therapy (PDT) has emerged as a promising cancer treatment modality; however, the potential molecular mechanisms remain obscure. Herein, we designed a near-infrared (NIR) light-activated nanoplatform (TPBC-PEG) to explore the therapeutic effects and mechanisms of PDT by using a model of intratibial primary and pulmonary metastasis osteosarcoma. Under laser irradiation, TPBC-PEG photosensitizer dose-dependently inhibited proliferative and metastatic capabilities while promoting apoptosis of osteosarcoma cells in vitro, and also effectively suppressed carcinogenesis and pulmonary metastasis in osteosarcoma xenograft mouse model. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis after high-throughput mRNA-seq indicated that the HIPPO signaling pathway was one of the 20 most significantly related signaling pathways. And a series of experiments for determining the HIPPO signaling activity were conducted to reconfirm the specificity. Collectively, PDT of TPBC-PEG micelles against carcinogenesis and pulmonary metastasis of deep-seated intratibial osteosarcoma was achieved by activating HIPPO signaling pathway. Our study identified a hitherto uncharacterized molecular mechanism of PDT, which may provide new insights to understand and design promising nanoplatforms for future cancer therapies.
研究领域:
肿瘤学
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分子生物学
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治疗学
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生物医学工程
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DOI
高影响因子
EUROPEAN POLYMER JOURNAL
·
2023
·
IF 6
Yuxin Wan,Zhenze Xie,Mingjie Wang,Yuelian Liu,Mubin Zheng,Dong Xu,Chang Du
Osteosarcoma (OS) is one of the most common primary bone malignancies in children and adolescents worldwide. The serious side effects and multi-drug resistance of high-dose chemotherapy have become the major cause of the failure in OS treatment. Curcumin (Cur) is reported to selectively kill OS cells and has a low cytotoxicity on healthy osteoblasts, but its delivery remains a great challenge. Herein, a co-polymer-Cur prodrug (co-prodrug) was developed by polymerizing Cur with hydrophilic polymer modified by succinic anhydride (SA) to explore the physicochemical properties, drug release and potential biological effects for OS treatment. This design endowed the co-prodrug with excellent solubility and stability under different solution conditions (pH = 4.5, 7.4 and 8.5), and improved the release efficiency of reactive oxygen species. Interestingly, co-prodrug exhibited an esterase-triggered rapid drug release in a concentration-dependent manner rather than the well-known acid response. Moreover, co-prodrug could be internalized into cells through endocytosis and significantly inhibit the proliferation of OS cells. Additionally, co-prodrug had no obvious systemic toxicity, and could suppress the OS growth by promoting apoptosis, inhibiting proliferation activity and vascularization in vivo. Our research furnishes a fresh perspective for the formulation design of controlled release of insoluble and instable anticancer agents within tumor cells.
研究领域:
药学
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肿瘤学
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药物递送系统
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癌症治疗
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DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Ying Fang,Yang Yu,Xiaoyan Jiang,Peilai Liu,Yu Chen,Wei Feng
Residual tumor cells and bone tissue defects are two critical challenges in clinical osteosarcoma treatment. Herein, a subnanomedicine concept is proposed by developing a self-adaptive functional tissue engineering scaffold constructed by integrating MoO 3− x subnanometric wires onto 3D printing bioactive glass scaffolds. The MoO 3− x subnanometric wires are synthesized by a one-pot hydrothermal method, which aggregate in an acidic tumor microenvironment and react with hydrogen peroxide to produce reactive oxygen species for specific chemodynamic therapy. However, they can degrade rapidly under physiological conditions without causing toxicity. Moreover, self-adaptively enhanced photothermal conversion enables tumor-targeting photothermal therapy while enhancing chemodynamic therapy. Additionally, the Mo 5+ -Mo 6+ transition enables lipid peroxide accumulation and glutathione depletion, thereby resulting in the deactivation of glutathione peroxidase 4 protein and ferroptosis through Western blot analysis, confocal laser scanning microscopy observation, and mRNA transcriptome analysis. In addition to its robustness against osteosarcoma, the constructed scaffolds can stimulate rat bone mesenchymal stem cell differentiation and proliferation as well as promote osteogenesis in bone defects. Therefore, this multifunctional scaffold not only validates the subnanomedicine concept but also provides a promising clinical strategy for bone tissue engineering.
研究领域:
生物医学工程
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材料科学
·
癌症研究
·
组织工程
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DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Xinglong Wang,Gongke Li,Ke Li,Yu Shi,Wenzheng Lin,Chun Pan,Dandan Li,Hao Chen,Jianwei Du,Huihui Wang
Targeted delivery of antitumor drugs has been recognized as a promising therapeutic modality to improve treatment efficacy, reduce the toxic side effects and inhibit tumor recurrence. In this study, based on the high biocompatibility, large specific surface area, and easy surface modification of small-sized hollow mesoporous silica nanoparticles β-cyclodextrin (β-CD)-benzimidazole (BM) supramolecular nanovalve, together with bone-targeted alendronate sodium (ALN) were constructed on the surface of small-sized HMSNs. The drug loading capacity and efficiency of apatinib (Apa) in HMSNs/BM-Apa-CD-PEG-ALN (HACA) were 65% and 25%, respectively. More importantly, HACA nanoparticles can release the antitumor drug Apa efficiently compared with non-targeted HMSNs nanoparticles in the acidic microenvironment of the tumor. In vitro studies showed that HACA nanoparticles exhibited the most potent cytotoxicity in osteosarcoma cells (143B cells) and significantly reduced cell proliferation, migration and invasion. Therefore, the drug-efficient release of antitumor effect of HACA nanoparticles is a promising way to treat osteosarcoma.
研究领域:
药理学
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纳米技术
·
肿瘤学
·
材料科学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2026
·
IF 5.4
Jinku Guo,Yingfeng Cao,Kaipen Jin,Bing Liu,Wei Wang,Chen Chen,Jun Xie,Ankai Xu
BackgroundCyclovirobuxine D (CVB-D), an alkaloid from Buxus microphylla, exhibits anticancer effects in various tumors, but its role in osteosarcoma remains unexplored. This study investigates its efficacy and mechanism in osteosarcoma.MethodsWe screened a drug library and evaluated CVB-D’s effects on osteosarcoma cell lines using CCK-8 and colony formation assays. Saos2 and K7M2 cells were selected for further analysis. Flow cytometry assessed apoptosis and cell cycle. RNA-seq identified downstream pathways, including NF-kappaB, and stemness markers (CD24, ALDH1A1). Stemness was examined via serum-free suspension culture, and NF-kappaB pathway activator Diprovocim was used in rescue experiments. A xenograft mouse model validated the findings.ResultsCVB-D suppressed proliferation, stemness, and induced apoptosis in osteosarcoma. These effects may be partially mediated through the p-NF-kappaB2/NF-kappaB2 axis and were reversible upon NF-kappaB pathway activation.ConclusionCVB-D inhibits osteosarcoma possibly via the non-canonical NF-kappaB pathway, suggesting a potential therapeutic strategy.
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PubMed
高影响因子
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